Amino acids thioacylation

The most suitable synthetic method for these products is the heterocyc-lization reaction of N-thioacyl derivatives of amino acids (202) with phosphorus tribromide (378, 442-450, 559, 560) or anhydrous trifluoroacetic acid (448, 449, 451, 452) (Scheme 103). Treatment of N-thioacyl amino acids with acetic anhydride leads directly to the thiazolylacetate without isolation of an intermediate thiazolinone (365. 452). 2-Alkoxy-derivatives of A-2-thiazoline-5-one, however, can be obtained without acetylation by this method (453, 454). 

Substituted 5-hydroxythiazoles (267b), Rj = alkylmercapto, acyl-amino, and sec-amino, are prepared by cydization of N-thioacyl-amino acids (266) with phosphorus tribromide or acetic anhydride (Scheme 137) (317, 350). i en the cydization of 266, R2 = H, is carried out with acetic anhydride in the presence of benzaldehyde (317, 325) or ethylformate (317), the benzylidene (268), R2=Ph, Rj = SR or CH2Ph, or 4-ethoxymethylene (268), Rj = SR and R2 = OEt, derivative is obtained directly (Scheme 138). 

Numerous variations of this reaction have been studied, principally those involving a prior inclusion of the nuclear sulfur atom in a thioacylamino compound. Thus, thiobenz-amido acetaldehyde diethyl acetal (8) underwent ring closure to 2-phenylthiazole (9) on gentle heating (57JCS1556). Similarly, iV-thioacyl a-amino acids also undergo ready ring closure to thiazoles. 

Coupling of Thioacylating Reagents with Amino Acids or Peptides ... 

Methyl thiocarboxylates are very suitable for the V-thioacylation of V-unprotected amino acids. Thus, shaking a heterogenous mixture of PhCSOMe in ether and the amino acid in aq. NaOH gives g(X)d yields of V-thiobenzoylated material. Using (9-alkyl thiocarboxylates of amino acids (2 R = R NHCHR ), the approach has been extended to synthesize endothiopeptides such as (5) formation of imidates may interfere with the desired process. The reaction has been carried out in water/THF using NazCOj or as shown in equation (3). ... 

Several uses of the reaction in equation (10) for the (V-thioacylation of amino acids, their esters, or amides have been reported. It is noteworthy that these reactions occur without racemization allowing a CD study of /V-thioacyl amino acids. Moreover, the reaction of equation (10) is not limited to amines or amino groups, but has also been employed to thioacylate hydrazines and hydroxylamines to give thiohydrazides and thiohydroxamic acids, respectively. 

Recently, a mild, efficient and racemization-free route for the incorporation of a thioamide linkage into a peptide either in solution or on solid phase was provided by Shalaby et al. [127], First, the N-Boc-amino acid anilide derivative was thionylated with P4St0 and subsequently activated by transformation to the benzotriazole derivative, affording a stable thioacylating reagent (Scheme 7.8) suitable for combinatorial syntheses. 

In an attempt to thioacylate 7-aminocephalosporanic acid (326) with hydroxycarbonylmethyl ATV-diethyldithiocarbamate in the presence of iodine-sodium iodide complex, Gottstein and his co-workers unexpectedly isolated iVTV-diethylcarbamoylmercaptomethylcephalosporin (327). This acylation reaction appeared to work also with other amino-acids, but always only in the presence of iodine. Not then realizing the actual role of... 

The [(thioacyl)hydrazino]triazines 554 were synthesized from 6-amino-5-hydrazino[l,2,4]triazines 552 by reaction with 553. Cyclization of 554 with an aqueous mineral acid gave (88S778) the triazinothiadiazine 555. 

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